A major effort by the LMO has been to elucidate the processes by which specific retroviral oncogenes, as well as their cellular homologs, are able to impact on critical cellular events. Using the avian retroviral oncogenes, ets and myc, as probes, we have detected, isolated, cloned and sequenced the cellular homologs of these genes from evolutionarily diverse organisms such as humans, mice, fish, sea urchin, Xenopus and Drosophila. There is a family of these proto-ets genes where specific regions of these cellular genes are retained at very high levels of homology; each of these proto-ets oncogenes was compared to their viral homologs. In all cases, the proto-oncogenes were much larger than their corresponding viral oncogenes. The consistent truncation of the viral oncogene and consequent alteration of its products implicates this type of damage as a general event that results in the disruption of the function of these highly conserved genes. We have also developed and exploited several expression vector systems, both prokaryotic and eukaryotic, to produce oncogene- specific products in quantity. These expressed products were used to purify, characterize and develop immunologic reagents to locate and characterize the cellular proto-oncogene products. Such reagents have also been used to probe for the expression of oncogene-specific products in normal and malignant tissues and related them to specific human pathologies. We have been able to isolate and characterize the gene products of ets and determine some relevant properties of this gene that implicate its function in the signal transduction pathway and in T4 cell maturation. It also seems that these proto-ets genes may play a significant role in Down's syndrome (DS), and may possibly be related to the higher than normal incidence of leukemic disease seen in DS patients.